The hypermethylation of MUC2 promoter associated with mRNA and metastasis in esophageal squamous cell carcinoma

Background: We evaluated the association between MUC2 methylation status and mRNA level in esophageal squamous cell carcinoma (ESCC) patients. Methods: The methylation index was examined by methylation-specific PCR and MUC2 mRNA was examined in paired tissue samples of 310 ESCC patients by real-time PCR. Results: The mean of MUC2 methylation index was 0.68 in ESCCs, and only 0.45 in non-tumor samples. There was a significant association between MUC2 methylation and lymph node metastasis, distant metastasis in ESCC. The lower level of MUC2 mRNA were in ESCC tissues (Mean(-Delta Ct)=-6.65), and higher in Non-tumor tissues (Mean(-Delta Ct)=-4.11). The lower MUC2 mRNA (-Delta Delta Ct(MUC2)<=-2.54) was 112/185 (60.54%) in ESCC with AJCC stage III-IV, 105/162 (64.81%) with N2-3 Lymph node metastasis, and 99/142 (69.72%) with differentiation G2. Meanwhile, the level of MUC2 mRNA were lower in ESCC patients with methylated promoter (Mean(-Delta Delta Ct)=-3.58) than those with hypomethylation (Mean(-Delta Delta Ct)=-0.32). And the ESCC patients with MUC2 silencing and hypermethylation in promoter had an unfavorable outcome. Conclusions: The results implied that the hypermethylation could be an important factor for silencing of MUC2 mRNA and a potential biomarker for poor survival in ESCC.